This proposal is concerned with the interactions between neurons and their target cells that govern synapse formation and maintenance. Primary emphasis is on the phenomenon of synaptic "repression", in which one synapse (often the more appropriate one) on a cell causes another to become functionally ineffective, without physically displacing it. This will be studied in the frog nerve-muscle preparation, where we have shown competitive interaction to occur, and where individual synapses or portions of synapses can be visualized and their microphysiology correlated with morphology at light and EM levels. It is hopes that this preparation will serve as a model for comparable phenomena occuring in the mammalian CNS, where individual recognized synapses cannot be studied. As an intermediate level between the neuromuscular junction and the CNS, we propose to look for synaptic repression in the ganglion cells, of the frog heart septum, and to elucidate the mechanisms of repression there as well. As a necessary background for understanding competition between synaptic inputs, we propose a systematic comparison of the properties of synapses formed by reinnervation of old endplates with those of junctions formed de novo by a regenerating nerve. We will seek to understand the basis for selective reinnervation of old synaptic sites and to correlate developmental stages in the physiology of terminals or portions of terminals with precise knowledge of the morphology of the specific structures studied. We will also continue our study of the trophic and inductive interactions between autonomic preganglionic nerves and skeletal muscle, with present emphasis on the morphological properties of these synapses, for correlation with physiological properties already determined.